The long-term objective of this research is to develop a technology and eventually a minimally-invasive commercial system for image-guided photodynamic therapy for cancer. This is certainly in keeping with NCI's focus on imaging in vivo for cancer screening, diagnosis, progression, image-guide therapy, treatment monitoring, and recurrence. In studies conducted at the University of Utah's Department of Pharmaceutics, Professor Lu's research team has designed and synthesized a bifunctional polymer containing an MRI contrast agent and a photosensitizer, and has demonstrated strong visualization of mouse tumors in MRI with the bifunctional conjugate, and good therapeutic efficacy when tumors were treated photodynamic therapy. ContraDyn, Inc. has licensed the technology which has allowed for this advance. Thus this proposal is a collaborative effort among the University of Utah, the inventor, and ContraDyn, Inc. Building on Professor Lu's work this proposal will incorporate a specific targeting agent to reduce the amount of chemicals to which people would be exposed. Challenges still to be met for photodynamic therapy include delivery of sufficient photosensitizer to target tissues, and accurate light-irradiation of the target. An efficient targeted drug-delivery system for both the photosensitizer and imaging probe is the ultimate goal of this program. Specifically, this grant would allow us to 1) design, synthesize, and characterize a tumor-specific targeted, bifunctional polymer; 2) evaluate the efficacy of the targeted, bifunctional polymer for tumor imaging and cancer treatment in a tumor-mouse model at several doses; and 3) optimize the synthesis and analytical methods for the safest formulation of the targeted, bifunctional polymer. PUBLIC HEALTH RELEVANCE: Photodynamic therapy has been shown to be an effective approach for treating cancers which are not accessible to surgery or are resistant to chemotherapy. Currently with photodynamic therapy it is difficult to remove, ablate, or treat tumor-tissue without harming the surrounding normal tissue. Addition of tumor-targeting agents and improved delivery systems should result in better outcomes and reduced damage to surrounding tissues. [unreadable] [unreadable] [unreadable]